title: Relatively high rates of G:C → A:T transitions at CpG sites were observed in certain epithelial tissues including pancreas and submaxillary gland of adult big blue® mice.
abstract: With few exceptions, spontaneous mutation frequency and pattern are similar across tissue types and relatively constant in young to middle adulthood in wild type mice. Underrepresented in surveys of spontaneous mutations across murine tissues is the diversity of epithelial tissues. For the first time, spontaneous mutations were detected in pancreas and submaxillary gland and compared with kidney, lung, and male germ cells from five adult male Big Blue® mice. Mutation load was assessed quantitatively through measurement of mutant and mutation frequency and qualitatively through identification of mutations and characterization of recurrent mutations, multiple mutations, mutation pattern, and mutation spectrum. A total of 9.6 million plaque forming units were screened, 226 mutants were collected, and 196 independent mutations were identified. Four novel mutations were discovered. Spontaneous mutation frequency was low in pancreas and high in the submaxillary gland. The submaxillary gland had multiple recurrent mutations in each of the mice and one mutant had two independent mutations. Mutation patterns for epithelial tissues differed from that observed in male germ cells with a striking bias for G:C to A:T transitions at CpG sites. A comprehensive review of lacI spontaneous mutation patterns in young adult mice and rats identified additional examples of this mutational bias. An overarching observation about spontaneous mutation frequency in adult tissues of the mouse remains one of stability. A repeated observation in certain epithelial tissues is a higher rate of G:C to A:T transitions at CpG sites and the underlying mechanisms for this bias are not known.
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Prtenjaca
authors.forename: Heather E
authors.initials: HE
authors.lastname: Tarnowski
authors.forename: Alison M
authors.initials: AM
authors.lastname: Marr
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Heney
authors.forename: Laura
authors.initials: L
authors.lastname: Creamer
authors.forename: Sarmitha
authors.initials: S
authors.lastname: Sathiamoorthy
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Hill
mesh_terms: D000818:Animals; D018899:CpG Islands; D007668:Kidney / Q000502:physiology; D056968:Lac Repressors / Q000235:genetics; D008168:Lung / Q000502:physiology; D008297:Male; D008822:Mice, Transgenic; D059645:Mutation Rate; D010179:Pancreas / Q000502:physiology*; D013363:Submandibular Gland / Q000502:physiology*
chemical_list: D056968:Lac Repressors
keywords: Big Blue® mice; kidney; lacI; lung; mutation pattern; mutation spectrum; pancreas; spontaneous mutation frequency; submaxillary gland; young adult